Genetic Regulation of Phospholipid Synthesis in Yeast

Abstract

In bakers yeast, Saccharomyces cerevisiae, a number of enzymes of phospholipid biosynthesis are regulated in a coordinated fashion. Evidence of coordinated regulation has come from a combination of biochemical and genetic studies carried out in a number of laboratories (3,4,9,10,13,16,18, 21). The enzymes subject to the regulation include: cytidine diphosphate diacylglycerol (CDP-DG) synthase, phosphatidylserine (PS) synthase; the phsopholipid N-methyltransferases (NMTs) which convert phosphatidylethanolamine (PE) to phosphatidylcholine (PC) and inositol-l-phosphate synthase (I1PS). These enzymes are repressed by the addition of inositol and choline to the growth medium and they respond to the same set of regulatory genes (9). The recent cloning (12,15) of two of the coordinately regulated structural genes, INO1 (structural gene for I1PS) and CHO1, (structural gene for PS synthase) as well as the isolation of a key regulatory gene, INO4, permits analysis of the regulation on a molecular level. The regulated expression of transcripts of the INO1 gene has recently been reported elsewhere (17). The CHO1 gene has been found to encode a single transcript of approximately 1.2kb. The steady state expression of this transcript correlates well with expression of the CHO1 gene product, PS synthase. The levels of transcript and enzyme subunit are both reduced in cells grown in the presence of inositol and choline. Growth in the presence of choline alone has no effect, but inositol alone leads to partial repression of the gene product and the transcript. PS synthase and the CHO1 transcript also exhibit altered expression in several regulatory mutants. The INO4 locus is known to be involved in the coordinated regulation of phospholipid synthesis in yeast (9,16). In ino4 mutants, I1PS and the NMTs are expressed only at the repressed level they cannot be derepressed). The levels of CHO1 transcript and PS synthase subunit are also reduced in ino4 cells. The INO4 gene has been cloned and several transcripts homologous to the cloned DNA have been detected.